Background
The myocardial kinetic energy (KE) and its association with pulmonary regurgitation (PR) have yet to be investigated in repaired tetralogy of Fallot (rTOF) patients.
Purpose
To evaluate ...the adaptation of myocardial KE in rTOF patients by tissue phase mapping (TPM).
Study Type
Prospective.
Population
A total of 49 rTOF patients (23 ± 5 years old; male = 32), 47 normal controls (22 ± 1 year old; male = 29).
Field Strength/Sequence
3‐T/2D dark‐blood three‐directional velocity‐encoded gradient‐echo sequence.
Assessment
Left and right ventricle (LV, RV) myocardial KE in radial (KEr), circumferential (KEø), longitudinal (KEz) directions. The proportions of KE in each direction to the sum of all KE (KErøz): %KEr, %KEø, %KEz. PR fraction.
Statistical Test
Student's t test, multivariable regression. Statistical significance: P < 0.05.
Results
In rTOF group, LV KEz remained normal in systole (P = 0.565) and diastole (P = 0.210), whereas diastolic LV %KEz (62% ± 14% vs. 72% ± 7%) and systolic LV %KEø (9% ± 6% vs. 20% ± 7%) were significantly decreased. The KEr and %KEr of both ventricles significantly increased in the rTOF group (RV in diastole: 6 ± 3 vs. 3 ± 1 μJ and 54% ± 13% vs. 27% ± 7%). The rTOF group exhibited significantly higher RV/LV ratios of %KEr (systole: 1.3 ± 0.3 vs. 1.0 ± 0.3) and %KEø (systole: 1.6 ± 0.8 vs. 1.0 ± 0.3) and significantly lower ratios of %KEz in systole (0.7 ± 0.2 vs. 1.0 ± 0.1) and diastole (0.5 ± 0.2 vs. 0.9 ± 0.1). In multivariable regression analysis, the RV peak systolic KErøz, RV systolic KEz, and LV diastolic %KEø were independently associated with PR fraction in the rTOF group (adjusted R2 = 0.479).
Data Conclusion
In rTOF patients, the adaptation of the KE proportion occurred earlier than that of the KE amplitude, and the biventricular balance of %KE was disrupted. PR may cause differential KE adaptation in RV and LV. TPM‐derived KE may be useful in investigation of myocardial adaptation in rTOF patients.
Evidence Level
2
Technical Efficacy
Stage 3
Kawasaki disease is the most common cause of acquired heart disease among febrile children under the age of 5 years old. It is also a clinically diagnosed disease. In this study, we developed and ...assessed a novel score system using objective parameters to differentiate Kawasaki disease from febrile children.
We analyzed 6,310 febrile children and 485 Kawasaki disease subjects in this study. We collected biological parameters of a routine blood test, including complete blood count with differential, C-reactive protein, aspartate aminotransferase, and alanine aminotransferase. Receiver operating characteristic curve, logistic regression, and Youden's index were all used to develop the prediction model. Two other independent cohorts from different hospitals were used for verification.
We obtained eight independent predictors (platelets, eosinophil, alanine aminotransferase, C-reactive protein, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and monocyte) and found the top three scores to be eosinophil >1.5% (score: 7), alanine aminotransferase >30 U/L (score: 6), and C-reactive protein>25 mg/L (score: 6). A score of 14 represents the best sensitivity value plus specificity prediction rate for Kawasaki disease. The sensitivity, specificity, and accuracy for our cohort were 0.824, 0.839, and 0.838, respectively. The verification test of two independent cohorts of Kawasaki disease patients (N = 103 and 170) from two different institutes had a sensitivity of 0.780 (213/273).
Our findings demonstrate a novel score system with good discriminatory ability for differentiating between children with Kawasaki disease and other febrile children, as well as highlight the importance of eosinophil in Kawasaki disease. Using this novel score system can help first-line physicians diagnose and then treat Kawasaki disease early.
In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the ...humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130–0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.
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•Establish CoVariant protein arrays including spike proteins from wild-type to omicron variants.•Concurrently detect neutralizing and binding antibodies against multiple SARS-CoV-2 variants.•Mixing of AZD1222 and mRNA-1273 generates better humoral immunity against omicron than matching.
Owing to the ongoing mutations of SARS-CoV-2, we developed an up-to-date CoVariant protein microarray to profile the humoral immunity. We collected plasmas from healthy subjects who underwent two doses of matching (AZD1222 ×2 or mRNA-1273 ×2) and two doses of mixing (AZD1222 + mRNA-1273). We found that mixing generates more surrogate neutralizing activity against gamma and omicron than matching. This study not only provides a high-throughput tool but also delivers a vaccine strategy to fight against SARS-CoV-2 mutations.
Asians have a higher carrier rate of pulmonary arterial hypertension (PAH)-related genetic variants than Caucasians do. This study aimed to identify PAH-related genetic variants using whole exome ...sequencing (WES) in Asian idiopathic and heritable PAH cohorts. A WES library was constructed, and candidate variants were further validated by polymerase chain reaction and Sanger sequencing in the PAH cohort. In a total of 69 patients, the highest incidence of variants was found in the BMPR2,
, and
genes. Regarding the
gene variants, there were two nonsense variants (c.994C>T, p. Arg332*; c.1750C>T, p. Arg584*), one missense variant (c.1478C>T, p. Thr493Ile), and one novel in-frame deletion variant (c.877_888del, p. Leu293_Ser296del). Regarding the
variants, there was one likely pathogenic nonsense variant (c.259C>T, p. Gln87*) and two missense variants (c.1207G>A, p. Val403Ile; c.38T>C, p. Leu13Pro). The
and
variant subgroups had worse hemodynamics. Moreover, the
variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL,
= 0.002) in comparison to the value in the non-
/non-
mutant group (267.8 ± 185.8 pg/mL). The
variant carriers had worse hemodynamics compared to the patients with the non-
/non-
mutant group. Moreover, there was a significantly lower GDF2 value in the
variant carriers compared to the control group.
may be a protective or corrected modifier in certain genetic backgrounds.
Because males have a higher KD incidence rate than do females, we further investigated whether the 10 miRNAs are significantly differentially expressed between male and female subjects, causing bias ...when served as a disease biomarker. The expressions of the remaining 9 biomarker miRNAs were not sex specific. ...we used the ΔCt values of the 10 miRNAs to develop a KD biomarker panel, training a Support Vector Machine (SVM) classification model, and diagnosing KD.
Coronary artery lesions (CAL) are a major complication of Kawasaki disease (KD). The early prediction of CAL enables the medical personnel to apply adequate medical intervention. We collected the ...serum samples from the KD patients with CAL (n = 32) and those without CAL (n = 31), followed by a global screening with isobaric tagging for relative and absolute quantification (iTRAQ) technology and specific validation with an enzyme-linked immunosorbent assay (ELISA). iTRAQ identified 846 proteins in total in the serum samples, and four candidate proteins related to CAL were selected for ELISA validation as follows: Protein S100-A4 (S100A4), Catalase (CAT), Folate receptor gamma (FOLR3), and Galectin 10 (CLC). ELISA validation showed that the S100A4 level was significantly higher in KD patients with CAL than in those without CAL (225.2 ± 209.5 vs. 143.3 ± 83 pg/mL, p < 0.05). In addition, KD patients with CAL had a significantly lower CAT level than those without CAL (1.6 ± 1.5 vs. 2.7 ± 2.3 ng/mL, p < 0.05). Next, we found that S100A4 treatment on human coronary artery endothelial cells (HCAECs) reduced the abundance of cell junction proteins, which promoted the migration of HCAECs. Further assays also demonstrated that S100A4 treatment enhanced the permeability of the endothelial layer. These results concluded that S100A4 treatment resulted in an incompact endothelial layer and made HCAECs more susceptible to in vitro neutrophil infiltration. In addition, both upregulated S100A4 and downregulated CAT increased the risk of CAL in KD. Further in vitro study implied that S100A4 could be a potential therapeutic target for CAL in KD.
Kawasaki disease (KD) typically occurs in children aged under 5 years and can cause coronary artery lesions (CALs). Early diagnosis and treatment with intravenous immunoglobulin can reduce the ...occurrence of CALs; therefore, identifying a good biomarker for diagnosing KD is essential. Here, using next-generation sequencing in patients with recurrent KD, those with viral infection, and healthy controls, we identified dysregulated circulating microRNAs as diagnostic biomarkers for KD. Pathway enrichment analysis illustrated the putative role of these miRNAs in KD progression. Their expression levels were validated using real-time polymerase chain reaction (qPCR). Fifteen dysregulated circulating miRNAs (fold changes >2 and <0.5) were differentially expressed in the recurrent KD group compared with the viral infection and control groups. These miRNAs were significantly involved in the transforming growth factor-β, epithelial-mesenchymal transition, and cell apoptosis signaling pathways. Notably, their expression levels were frequently restored after intravenous immunoglobulin treatment. Among the candidates, miR-24-3p expression level was significantly higher in patients with recurrent KD compared with healthy controls or viral infection controls (
< 0.001). Receiver operating characteristic analysis revealed that high miR-24-3p expression levels may be a potential biomarker for KD diagnosis. In conclusion, we identified miR-24-3p significantly higher in KD patients, which may be a potential diagnostic biomarker for KD.
Background The myocardial adaptive mechanism in patients with repaired tetralogy of Fallot (rTOF) is less understood. We aimed to investigate biventricular myocardial adaptive remodeling in rTOF ...patients. Methods We recruited 32 rTOF patients and 38 age- and sex-matched normal controls. The pulmonary stenosis of rTOF patients was measured using catheterized pressure gradient between right ventricle (RV) and pulmonary artery (PG.sub.RVPA). rTOF patients with PG.sub.RVPA 15 mmHg and greater than or equal to15 mmHg were classified as low pulmonary stenosis (rTOF.sub.low, n = 19) and high pulmonary stenosis (rTOF.sub.high, n = 13) subgroups, respectively. Magnetic resonance imaging tissue phase mapping was employed to evaluate the voxelwise biventricular myocardial motion in longitudinal (Vz), radial (Vr), and circumferential (Vphi) directions. Results The rTOF.sub.low subgroup presented higher pulmonary regurgitation fraction than rTOF.sub.high subgroup (p 0.001). Compared with the normal group, only rTOF.sub.low subgroup presented a decreased RV ejection fraction (RVEF) (p 0.05). The rTOF.sub.low subgroup showed decreased systolic and diastolic Vz in RV and LV, whereas rTOF.sub.high subgroup showed such change only in RV. In rTOF.sub.low subgroup, RVEF significantly correlated with RV systolic Vr (r = 0.56, p 0.05), whereas LVEF correlated with LV systolic Vz (r = 0.51, p = 0.02). Prolonged QRS correlated with RV systolic Vr (r = -0.58, p 0.01) and LV diastolic Vr (r = 0.81, p 0.001). No such correlations occurred in rTOF.sub.high subgroup. Conclusions The avoidance of unfavorable functional interaction in RV and LV in rTOF.sub.high subgroup suggested that adequate pulmonary stenosis (PG.sub.RVPA greater than or equal to 15 mmHg in this sereis) has a protective effect against pulmonary regurgitation.
Objectives
We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function.
...Methods
We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VØ) directions in basal, middle, and apical slices. The VØ peak-to-peak (PTP) during systolic phases, the rotation angle of each slice, and VØ inconsistency were computed for evaluating LV twist function and VØ dyssynchrony.
Results
As compared to the controls, the rTOF patients presented decreased RV ejection fraction (RVEF) (
p
= 0.002) and preserved global LV ejection fraction (LVEF). They also demonstrated decreased systolic and diastolic Vz in several LV segments and higher diastolic Vr in the septum (all
p
< 0.05). A lower VØ PTP, higher VØ inconsistency, and reduced peak net rotation angle (all
p
< 0.05) were observed. The aforementioned indices demonstrated an altered LV twist function in rTOF patients in an early disease stage.
Conclusions
MR TPM could provide information about early abnormalities of LV regional motion and twist function in rTOF patients with preserved LV global function.
Key points
•
Patients with rTOF presented significantly reduced systolic and diastolic Vz in the LV
.
•
rTOF patients demonstrated significantly increased diastolic Vr in the septum
.
•
Abnormal characteristics of the segmental dynamic velocity evolution were shown in rTOF
.
•
rTOF patients presented altered circumferential rotation and velocity inconsistency in early stage
.
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